人类 GDAP1 基因的表观遗传调控

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry and Biophysics Reports Pub Date : 2024-09-19 DOI:10.1016/j.bbrep.2024.101827
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引用次数: 0

摘要

神经节苷脂诱导分化相关蛋白 1(GDAP1)基因突变与夏科-玛丽-牙(CMT)病(一种遗传性神经退行性疾病)有关。该基因编码的蛋白质参与线粒体分裂和钙平衡。最近,GDAP1 还与某些癌症患者的存活率有关。尽管 GDAP1 在特定细胞过程和相关疾病中发挥着重要作用,但其表达调控机制在很大程度上仍不为人所知。在这里,我们首次发现 GDAP1 基因近端启动子 CpG 岛的甲基化会抑制其活性。使用甲基转移酶和 HDAC 抑制剂处理 GDAP1 低表达的细胞,可诱导该基因及其编码蛋白的表达。这种诱导与启动子去甲基化和乙酰化组蛋白与 GDAP1 启动子的结合增加有关。因此,我们发现了一种可用于操纵 GDAP1 表达的机制。
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Epigenetic regulation of the human GDAP1 gene

Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are linked to Charcot–Marie–Tooth (CMT) disease, a hereditary neurodegenerative condition. The protein encoded by this gene is involved in mitochondrial fission and calcium homeostasis. Recently, GDAP1 has also been implicated in the survival of patients with certain cancers. Despite its significant role in specific cellular processes and associated diseases, the mechanisms regulating GDAP1 expression are largely unknown. Here, we show for the first time that methylation of the CpG island in the proximal promoter of the GDAP1 gene inhibits its activity. Treating cells with low GDAP1 expression using methyltransferase and HDAC inhibitors induced the expression of this gene and its encoded protein. This induction was associated with promoter demethylation and increased association of acetylated histones with the GDAP1 promoter. Thus, we identified a mechanism that could be used to manipulate GDAP1 expression.

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来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
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